From β-Blasts to α-Bombs: Bone-Targeting Radiopharmaceutical Therapies

Bone metastases are a significant source of morbidity in advanced malignancy, particularly in prostate cancer, because osteoblastic metastases can cause pain, skeletal-related events, and quality-of-life impairment. Bone-targeting radionuclide drugs are also effective in the treatment of increased bone turnover and were first developed as β-emitters for palliation but have been developed in recent years as α-emitters with proven survival benefit. This review covers the biology, history, and mechanism of action of the approved bone-targeting radiopharmaceuticals (89Sr-chloride, 153Sm-lexidronam, 223Ra-dichloride). Special focus is placed on the only bone-targeting radiopharmaceutical currently approved in the United States—223Ra-dichloride—including patient selection, administration, radiation safety, and follow-up. 223Ra, a calcium analog with a short α-particle path length, high linear energy transfer, and marrow-sparing properties, is valuable in the treatment of metastatic androgen pathway modulator–resistant prostate cancer (formerly metastatic castration-resistant prostate cancer) with bone-predominant disease and symptoms. The practical aspects of nuclear medicine are emphasized, such as imaging confirmation, laboratory value thresholds, written instructions, room preparation, contamination control, discharge instructions, and posttreatment monitoring. Bone-targeting radiopharmaceutical therapy has increasingly attractive options beyond palliation with new combination and sequencing treatment options involving prostate-specific membrane antigen–targeted therapy. The lessons learned from the shift from “β-blasts” to “α-bombs” provide a potential pathway to more effective current treatment and a new generation of targeted radiopharmaceutical therapy.